chr10-20880891-T-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_006393.3(NEBL):c.383A>T(p.Gln128Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00007 in 1,614,058 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_006393.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000460 AC: 70AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000115 AC: 29AN: 251328Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135830
GnomAD4 exome AF: 0.0000287 AC: 42AN: 1461762Hom.: 1 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 727182
GnomAD4 genome AF: 0.000466 AC: 71AN: 152296Hom.: 0 Cov.: 32 AF XY: 0.000430 AC XY: 32AN XY: 74462
ClinVar
Submissions by phenotype
not specified Uncertain:2
Variant classified as Uncertain Significance - Favor Benign. The p.Gln128Leu var iant in NEBL has not been previously reported in individuals with cardiomyopathy , but has been identified in 0.2% (19/10400) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs139809958 ). Computational prediction tools and conservation analysis do not provide stron g support for or against an impact to the protein. In summary, while the clinica l significance of the p.Gln128Leu variant is uncertain, its frequency suggests t hat it is more likely to be benign. -
The c.383A>T (p.Q128L) alteration is located in exon 5 (coding exon 5) of the NEBL gene. This alteration results from a A to T substitution at nucleotide position 383, causing the glutamine (Q) at amino acid position 128 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
A variant of uncertain significance has been identified in the NEBL gene. The Q128L variant has not been published as pathogenic or been reported as benign to our knowledge. The Q128L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved across species. Furthermore, in silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in the same residue (Q128R) has been reported in association with DCM and endocardial fibroelastosis in a newborn (Purevjav et al., 2010); however the pathogenicity of this variant has not been definitively determined. Nevertheless, this variant has been observed in approximately 0.2% of alleles from individual of African ancestry in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server; Exome Aggregation Consortium). -
Primary dilated cardiomyopathy Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at